Gonadotropin-releasing hormone agonist downregulation combined with hormone replacement therapy improves the reproductive outcome in frozen-thawed embryo transfer cycles for patients of advanced reproductive age with idiopathic recurrent implantation failure.

The live birth rate in the GnRH agonist-HRT group was significantly higher than in both the HRT group and NC group.

• Live birth rate was 36.55% in the GnRH agonist-HRT group, 22.16% in the HRT group, and 16.92% in the NC group (P < 0.0001).
• Study included 549 older patients (aged 36-43 years) with idiopathic recurrent implantation failure across three groups: NC (n=65), HRT (n=194), and GnRH agonist-HRT (n=290).
• Data were collected over a 5-year period (January 2015-December 2020) at Northwest Women's and Children's Hospital.
• All patients were undergoing their third cleavage-stage embryo or blastocyst transfer after IVF/ICSI cycles.

After adjusting for potential confounders, logistic regression confirmed that the GnRH agonist-HRT group had significantly higher live birth rates than both comparison groups.

• Compared to the HRT group, the odds ratio for live birth in the GnRH agonist-HRT group was 0.594 (95% CI: 0.381-0.926; P=0.021).
• Compared to the NC group, the odds ratio for live birth in the GnRH agonist-HRT group was 0.380 (95% CI: 0.181-0.796; P=0.010).
• The logistic regression model adjusted for potential confounding variables.
• The primary outcome measure was live birth rate; secondary outcomes included clinical pregnancy rate, miscarriage rate, and ongoing pregnancy rate.

Patients with known endometriosis or adenomyosis were excluded from the study to focus on idiopathic recurrent implantation failure.

• The study was a retrospective cohort design involving 549 older patients.
• Recurrent implantation failure was defined as idiopathic, excluding patients with endometriosis or adenomyosis.
• All patients had failed at least two prior embryo transfers, being on their third transfer cycle.
• The study population was limited to women aged 36-43 years, representing advanced reproductive age.

The authors hypothesize that the GnRH agonist-HRT protocol enhances implantation-related factors and promotes optimal endometrial receptivity.

• The proposed mechanism involves enhancement of implantation-related factors leading to improved endometrial receptivity.
• The authors note these findings are useful for further investigating the underlying mechanism of the GnRH agonist-HRT protocol in improving reproductive outcomes.
• Patients with known causes of implantation failure (endometriosis, adenomyosis) were excluded, suggesting the protocol may address otherwise unexplained endometrial factors.
• The study does not directly measure endometrial receptivity markers but infers improved receptivity from clinical outcomes.